This invention relates to non-viral gene delivery carriers. More particularly, this invention relates to high molecular weight arginine-conjugated bioreducible poly (disulfide amine) polymers (ABP) as gene delivery carriers.
Gene therapy offers the potential to treat human congenital and acquired diseases using therapeutic gene-based drugs. One of the requirements for successful gene therapy is the development of non-toxic and efficient carriers for gene delivery. Compared to viral vectors, non-viral gene carriers such as lipids, synthetic polymers and/or peptides offer a number of advantages including easy and large-scale production, non-immunogenicity, flexible DNA and RNA loading capacity and stability among others. Despite these advantages, however, the widespread adoption of non-viral gene vectors has been limited by concerns related to cytotoxicity and decreased transfection efficiency. However, since the accumulation of non-degraded polymers inside cells is often the cause of cytotoxicity, the biodegradation of polymers after efficient transfection of DNA can reduce or eliminate this problem. Biodegradable polymers typically contain ester or disulfide-bonds. Ester bonds, however, are easily hydrolyzed in the extracellular environment, while disulfide bonds are typically more stable, as they are not reduced until they are exposed to glutathione (GSH) in the intracellular cytoplasm. Based on these considerations, several types of bio-reducible polymers containing disulfide bonds have been developed.